Rfam Coronavirus Special Release

In response to the SARS-CoV-2 outbreak, the Rfam team prepared a special release dedicated to the Coronavirus RNA families. The release 14.2 includes 10 new and 4 revised families that can be used to annotate the SARS-CoV-2 and other Coronavirus genomes with RNA families.

View the data at rfam.org/covid-19 ➡️

New Coronavirus Rfam families

In collaboration with the Marz group and the EVBC, we created 10 families representing the entire 5’- and 3’- untranslated regions (UTRs) for Alpha-, Beta-, Gamma-, and Delta- coronaviruses. A specialised set of alignments for the subgenus Sarbecovirus is also provided, including the SARS-CoV-1 and SARS-CoV-2 UTRs. 

The families are based on a set of high-quality whole genome alignments produced with LocARNA and reviewed by expert virologists. Note that the Alpha-, Beta-, and Deltacoronavirus alignments and structures were refined based on the literature, while the Gammacoronavirus families are based on prediction alone due to the lack of experimental data.

Virus	5’ UTR	3’ UTR
Alphacoronavirus	aCoV-5UTR RF03116	aCoV-3UTR RF03121
Betacoronavirus	bCoV-5UTR RF03117	bCoV-3UTR RF03122
Sarbecovirus and SARS-CoV-2	Sarbecovirus-5UTR RF03120	Sarbecovirus-3UTR RF03125
Gammacoronavirus	gCoV-5UTR RF03118	gCoV-3UTR RF03123
Deltacoronavirus	dCoV-5UTR RF03119	dCoV-3UTR RF03124

Previously, only fragments of the UTRs were found in Rfam. In particular, two families were superseded by the new whole-UTR alignments and removed from Rfam:

• RF00496 (Coronavirus SL-III cis-acting replication element): This family represented a single stem that is now found in aCoV-5UTR and bCoV-5UTR families.
• RF02910 (Coronavirus_5p_sl_1_2): This family represented two stems from aCoV-5UTR.

The new families are grouped into 2 clans: CL00116 and CL00117 for the 5’ and 3’ UTRs, respectively. The clans can be used with the Infernalcmscan program to automatically select the highest scoring match from a set of related families (see the Rfam chapter in CPB to learn more).

Revised Coronavirus families

We also reviewed and updated the existing Coronavirus Rfam families.

Family	What was updated?	Is it found in SARS-CoV-2?
RF00182 Coronavirus packaging signal	The seed alignment and consensus secondary structure were updated to include the 4 conserved repeat units.	This RNA element isfound only in Embecovirus, so it is not present in SARS-CoV-2 and other Sarbecoviruses.
RF00507 Coronavirus frameshifting stimulation element	The seed alignment was expanded.	This RNA is present in SARS-CoV-2.
RF00164 Coronavirus s2m RNA	The seed alignment was expanded. There is a 3D structure for SARS-CoV-1 which can be used for understanding the s2m in SARS-CoV-2.	This RNA is present in the 3′ UTR of SARS-CoV-2.
RF00165 Coronavirus 3’-UTR pseudoknot	The seed alignment was expanded.  The pseudoknot is annotated in the 3’ UTR families but since it is mutually exclusive with the 3’-UTR consensus structure, it is also provided as a separate family.	This RNA is present in the 3′ UTR of SARS-CoV-2.

Where to get the data 

You can download the covariance models, as well as seed alignments for the coronavirus families from the corresponding family pages or from a dedicated folder on the FTP archive.

How to use the data

You can download the covariance models and annotate viral sequences with these RNA models using Infernal. See Rfam help for examples.

Inviting all Wikipedians to contribute

We revised the Wikipedia pages associated with each family, and we invite everyone to contribute to the following articles:

• Coronavirus 5′ UTR
• Coronavirus 3′ UTR
• Coronavirus packaging signal
• Coronavirus 3′ UTR pseudoknot
• Coronavirus frameshifting stimulation element
• Coronavirus 3′ stem-loop II-like motif (s2m)

Acknowledgements

We would like to thank Kevin Lamkiewicz and Manja Marz (Friedrich Schiller University Jena) for providing the curated alignments for the new families as well as Eric Nawrocki (NCBI) for revising the existing Rfam entries. We also thank Ramakanth Madhugiri (Justus Liebig University Giessen) for reviewing the Coronavirus UTR alignments.

This work is part of the BBSRC-funded project to expand the coverage of viral RNAs in Rfam. More data on SARS-CoV-2 can be found on the European COVID-19 Data Portal.